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Pflugers Arch
2015 Dec 01;46712:2423-35. doi: 10.1007/s00424-015-1709-1.
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Heterologous expression of NaV1.9 chimeras in various cell systems.
Goral RO, Leipold E, Nematian-Ardestani E, Heinemann SH.
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SCN11A encodes the voltage-gated sodium channel NaV1.9, which deviates most strongly from the other eight NaV channels expressed in mammals. It is characterized by resistance to the prototypic NaV channel blocker tetrodotoxin and exhibits slow activation and inactivation gating. Its expression in dorsal root ganglia neurons suggests a role in motor or pain signaling functions as also recently demonstrated by the occurrence of various mutations in human SCN11A leading to altered pain sensation syndromes. The systematic investigation of human NaV1.9, however, is severely hampered because of very poor heterologous expression in host cells. Using patch-clamp and two-electrode voltage-clamp methods, we show that this limitation is caused by the C-terminal structure of NaV1.9. A chimera of NaV1.9 harboring the C terminus of NaV1.4 yields functional expression not only in neuronal cells but also in non-excitable cells, such as HEK 293T or Xenopus oocytes. The major functional difference of the chimeric channel with respect to NaV1.9 is an accelerated activation and inactivation. Since the entire transmembrane domain is preserved, it is suited for studying pharmacological properties of the channel and the functional impact of disease-causing mutations. Moreover, we demonstrate how mutation S360Y makes NaV1.9 channels sensitive to tetrodotoxin and saxitoxin and that the unusual slow open-state inactivation of NaV1.9 is also mediated by the IFM (isoleucine-phenylalanine-methionine) inactivation motif located in the linker connecting domains III and IV.
Black,
Nav1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus.
2014, Pubmed
Black,
Nav1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus.
2014,
Pubmed Blum,
Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9.
2002,
Pubmed Catterall,
Voltage-gated sodium channels at 60: structure, function and pathophysiology.
2012,
Pubmed Choi,
Functional role of the C-terminus of voltage-gated sodium channel Na(v)1.8.
2004,
Pubmed Coste,
Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons.
2004,
Pubmed Cummins,
A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons.
1999,
Pubmed Dib-Hajj,
NaN/Nav1.9: a sodium channel with unique properties.
2002,
Pubmed Dib-Hajj,
NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy.
1998,
Pubmed Djouhri,
The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons.
2003,
Pubmed Favre,
Specificity for block by saxitoxin and divalent cations at a residue which determines sensitivity of sodium channel subtypes to guanidinium toxins.
1995,
Pubmed
,
Xenbase Heinemann,
Calcium channel characteristics conferred on the sodium channel by single mutations.
1992,
Pubmed
,
Xenbase Heinemann,
Molecular basis for pharmacological differences between brain and cardiac sodium channels.
1992,
Pubmed Huang,
Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy.
2014,
Pubmed Jurman,
Visual identification of individual transfected cells for electrophysiology using antibody-coated beads.
1994,
Pubmed Lawrence,
Single-channel analysis of inactivation-defective rat skeletal muscle sodium channels containing the F1304Q mutation.
1996,
Pubmed
,
Xenbase Lee,
Role of the terminal domains in sodium channel localization.
2009,
Pubmed
,
Xenbase Lee,
Role of the amino and carboxy termini in isoform-specific sodium channel variation.
2008,
Pubmed
,
Xenbase Leipold,
A de novo gain-of-function mutation in SCN11A causes loss of pain perception.
2013,
Pubmed Leipold,
Molecular determinants for the subtype specificity of μ-conotoxin SIIIA targeting neuronal voltage-gated sodium channels.
2011,
Pubmed Miloushev,
Solution structure of the NaV1.2 C-terminal EF-hand domain.
2009,
Pubmed Nguyen,
Sodium channel carboxyl-terminal residue regulates fast inactivation.
2010,
Pubmed
,
Xenbase Ojha,
Sodium channels as gateable non-photonic sensors for membrane-delimited reactive species.
2014,
Pubmed Ostman,
GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9.
2008,
Pubmed Patino,
Electrophysiology and beyond: multiple roles of Na+ channel β subunits in development and disease.
2010,
Pubmed Plummer,
Evolution and diversity of mammalian sodium channel genes.
1999,
Pubmed Priest,
Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior.
2005,
Pubmed Reddy Chichili,
Structural basis for the modulation of the neuronal voltage-gated sodium channel NaV1.6 by calmodulin.
2013,
Pubmed Roy,
Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons.
1992,
Pubmed Rugiero,
Selective expression of a persistent tetrodotoxin-resistant Na+ current and NaV1.9 subunit in myenteric sensory neurons.
2003,
Pubmed Satin,
A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.
1992,
Pubmed
,
Xenbase Schlief,
Pore properties of rat brain II sodium channels mutated in the selectivity filter domain.
1996,
Pubmed
,
Xenbase Sivilotti,
A single serine residue confers tetrodotoxin insensitivity on the rat sensory-neuron-specific sodium channel SNS.
1997,
Pubmed
,
Xenbase Spampanato,
A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for beta subunit interaction.
2004,
Pubmed
,
Xenbase Subramanian,
Role of Na(v)1.9 in activity-dependent axon growth in motoneurons.
2012,
Pubmed Tombola,
How does voltage open an ion channel?
2006,
Pubmed Trimmer,
Primary structure and functional expression of a mammalian skeletal muscle sodium channel.
1989,
Pubmed
,
Xenbase Vanoye,
Mechanism of sodium channel NaV1.9 potentiation by G-protein signaling.
2013,
Pubmed Vijayaragavan,
The C-terminal region as a modulator of rNa(v)1.7 and rNa(v)1.8 expression levels.
2004,
Pubmed Walker,
Marked difference in saxitoxin and tetrodotoxin affinity for the human nociceptive voltage-gated sodium channel (Nav1.7) [corrected].
2012,
Pubmed West,
A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.
1992,
Pubmed
,
Xenbase Wetzel,
Cell-autonomous axon growth of young motoneurons is triggered by a voltage-gated sodium channel.
2013,
Pubmed Zhang,
A carboxy-terminal alpha-helical segment in the rat skeletal muscle voltage-dependent Na+ channel is responsible for its interaction with the amino-terminus.
2000,
Pubmed Zhang,
Gain-of-function mutations in SCN11A cause familial episodic pain.
2013,
Pubmed
